Clinical Trial of Expanded and Activated Autologous NK Cells to Treat Multiple Myeloma

NCT02481934 | Completed Phase 1 Results

• 1 other identifier: NK-VS-MM
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine wether activated and expanded autologous Natural Killer cells (NKAEs) are effective in the treatment of patients with multiple myeloma on second or later relapse. NKAEs are used in combination with anti-myeloma drugs such as lenalidomide or bortezomib.

Conditions

Multiple Myeloma

Keywords

Recurrent multiple myeloma; NK cells; cell therapy; NKAE; Relapsed multiple myeloma

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events During NKAE Treatment

  Toxicity will be assessed by adverse events count during NKAE treatment monitoring peripheral blood absolute neutrophil count (cells/μl). Toxicity will be evaluated monthly during NKAE treatment (4 months). During follow-up, it will be assessed monthly the first 6 months. After that, quarterly until one year of follow-up, based on Common Toxicity Criteria for Adverse Events of the National Cancer Institute (CTCAE) to v.4.03.

  16 months

Secondary Outcomes (1)

• Number of Participants With Peripheral Blood Monoclonal Protein Reduction or Stabilization

  16 months

Study Arms (1)

NKAE cells infusion + chemotherapy

EXPERIMENTAL

Expanded and activated autologous NK cells (NKAEs) + chemotherapy (lenalidomide OR bortezomib).

Procedure: NKAE cells infusion; Drug: Lenalidomide; Drug: Bortezomib

Interventions

NKAE cells infusion PROCEDURE

Expanded and activated autologous NK cells infusion. Each patient will receive two infusions of 7.5 x 106 expanded and activated autologous NK cells/kg/cycle.

Also known as: NKAE infusion, Activated and expanded autologous NK cells infusion

NKAE cells infusion + chemotherapy

Lenalidomide DRUG

Lenalidomide, 10 mg oral/day during 21 days (cycle). Patients will receive 4 cycles.

Also known as: Revlimid

NKAE cells infusion + chemotherapy

Bortezomib DRUG

Bortezomib, 1.3 mg/m2, s.c., days 1, 4, 8 and 11/cycle. Patients will receive 4 cycles.

Also known as: Velcade

NKAE cells infusion + chemotherapy

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects between 20 and 80 years old
• With multiple myeloma in 2nd or later relapse or showing resistance after 2 treatment lines
• Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Life expectancy greater than six months
• Creatinine clearance rate more than 30 ml / min
• Subjects who have received at least 4 cycles of rescue treatment under the procedures of the 12 de Octubre Hospital (rescue treatment will vary depending on previous anti-myeloma treatment). After treatment, patients must have shown chemosensitivity and disease stabilization.
• Will be included subjects with partial response or stable disease (for at least 2 cycles) after 75% of planned rescue treatment or patients at subclinical progression (defined as an increase of monoclonal component ≥ 25%) at any time of rescue treatment. Subjects have to show tolerance to rescue treatment, without G3/4 adverse effects, if G1/2 adverse effects exist they must be analyzed immediately before starting reinfusion program.
• Subjects have to agree to participate in the trial and they have to sign informed consent.

You may not qualify if:

• Subjects with clinical progression or complete response will not be included.
• Any of the following abnormal laboratory results:
• Absolute Neutrophil Count \< 1000/ µL Platelets Count \< 50000/ µL in those patients with bone marrow infiltration lower than 50% Measured creatinine clearance \<30 ml/min Hemoglobin level ≤ 8 g/dL Peripheral neuropathy ≥ Grade 2
• Subjects have received allogeneic stem cell transplant.
• Subjects with heart disease which compromises patient's life or protocol accomplishment.
• Subjects with past clinical history of malignant disease within 3 years (exceptions are squamous or basal cell carcinoma).
• Subjects receiving another investigational drug or having received investigational drug within 30 days before screening.
• Subjects who require chronic steroid or immunosuppressive treatment.
• Any condition, including abnormally laboratory results, that might compromise the patient´s life if he participate in this study.
• Any concurrent medical condition, abnormally laboratory results or any psychological disorder that prevent the patient to sign the informed consent.
• Pregnant or fertile women.
• Patients known to be seropositive for human immunodeficiency virus (VIH) or having active hepatitis A, B or C.

Sponsors & Collaborators

• Joaquín Martínez López, MD, PhD: lead
• Hospital Infantil Universitario Niño Jesús, Madrid, Spain: collaborator

Study Sites (1)

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Lenalidomide; Bortezomib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines

Limitations and Caveats

Volume of the peripheral blood from patients was limiting in order to perform different cohorts with more NKAE cells infusions.

Results Point of Contact

• Title: Alejandra Leivas PhD
• Organization: Hospital universitario 12 de octubre

alejandraleial@gmail.com

+34917792612

Study Officials

• Joaquín Martínez López, M.D, Ph.D

  Hospital Universitario 12 de Octubre

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Hematology Head of department, M.D., Ph.D.

Study Record Dates

• First Submitted: June 10, 2015
• First Posted: June 25, 2015
• Study Start: March 1, 2013
• Primary Completion: July 1, 2016
• Study Completion: October 1, 2016
• Last Updated: August 20, 2021
• Results First Posted: December 5, 2016

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)